Identification and functional regulation of three alternative splicing isoforms of the Ythdc2 gene in Miichthys miiuy

Abstract

Alternative splicing is an important process in the post-transcriptional processing of mRNA. Different alternative splicing isoforms of the same gene may encode proteins with different structures and functions.Ythdc2 gene is a kind of ATPase with RNA helicase activity, and its YTH domain can recognize and bind RNA molecules containing m⁶A methylation site, thus playing a regulatory role. Many studies have shown that the Ythdc2 gene is important in tumorigenesis and non-neoplastic diseases. However, there were few studies on the alternative splicing events of the Ythdc2 gene. Therefore, this study identified three alternative splicing isoforms of the Ythdc2 gene in Miichthys miiuy. We named them Ythdc2-α, Ythdc2-β, and Ythdc2-γ. The results showed that only Ythdc2-α had a YTH domain, and the other two alternative splicing isoforms Ythdc2-β and Ythdc2-γ lacked the YTH domain. Under the stimulation of LPS, the expression levels of three alternative splicing isoforms showed an upward trend. Moreover, these three alternative splicing isoforms might have had different regulatory effects on the expression of inflammatory factors, which could negatively regulate the innate immune response and inhibit the NF-κB and IRF3 signaling pathways, providing new evidence for the role of Ythdc2 in fish innate immune response.